MOF composite material and preparation method thereof

Abstract

The invention discloses an MOF composite material and a preparation method thereof. The MOF composite material comprises a metal organic framework material MIL-100 (Fe) and a loaded drug, the loaded drug is loaded on the metal organic framework material MIL-100 (Fe) to form a nano-carrier composite material MHB NPs, and the loaded drug comprises hypocrellin HB or a derivative of hypocrellin HB. The MOF composite material takes a metal organic framework material MIL-100 (Fe) as a drug carrier, and hypocrellin B HB or a derivative of hypocrellin B is loaded on the drug carrier to form a nano-carrier composite material MHB NPs, so that the treatment of tumor cells by adopting red light is facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of metal-organic materials, and particularly relates to a MOF composite material and a preparation method thereof. Background Art

[0002] Metal-Organic Frameworks (MOFs) are porous materials with a three-dimensional structure composed of metal ions or metal clusters and organic ligands. They have a large specific surface area, diverse compositions, adjustable pore structures, and can be chemically modified as needed. They have shown great advantages in many fields such as energy storage, gas adsorption and separation, catalysis, and sensing, and have great application prospects.

[0003] The MIL series of materials is a type of MOF materials. Among them, MIL-100(Fe) has excellent thermal stability, adsorption performance, and photocatalytic performance, and remains structurally stable even after being exposed to boiling water for several weeks. It is one of the thermodynamically stable MOF materials. The existing MOF composite materials formed by MIL-100(Fe) materials have limited functions and cannot meet the growing demand for tumor treatment. Summary of the Invention

[0004] In view of the above-mentioned defects or deficiencies in the prior art, it is desired to provide a MOF composite material and a preparation method thereof.

[0005] In the first aspect of the present invention, a MOF composite material is provided, including: a metal-organic framework material MIL-100(Fe) and a drug carrier. The drug carrier is loaded on the metal-organic framework material MIL-100(Fe) to form a nanocarrier composite material MHB NPs. The drug carrier includes hypocrellin B (HB) or a derivative of hypocrellin B.

[0006] In addition, the MOF composite material of the present invention may also have the following additional technical features: Preferably, the structural formula of hypocrellin B (HB) is:

[0007] The derivatives of hypocrellin B include: derivative HB1 or derivative HB2, and the structural formulas of derivative HB1 and derivative HB2 are:

[0008] Among them, Me is methyl.

[0009] Preferably, the drug loading amount of the drug carrier is 20% to 40%, where the drug loading amount of the drug carrier is the mass ratio of the drug carrier in the nanocarrier composite material MHB NPs.

[0010] Preferably, the average particle size of the metal-organic framework material MIL-100(Fe) is 200-230 nm; the average particle size of the nanocarrier composite material MHB NPs is 230-250 nm.

[0011] Preferably, the MOF composite material further comprises a targeted drug, and the targeted drug is coated on the surface of the nanocarrier composite material MHB NPs. The targeted drug includes hyaluronic acid, folic acid or the targeting peptide RGD.

[0012] Preferably, the mass ratio of the metal-organic framework material MIL-100(Fe) to the hyaluronic acid is 1:(0.25-1.5); Or, The mass ratio of the nanocarrier composite material MHB NPs to the targeting peptide RGD is (3-8):(0.5-2).

[0013] Preferably, the hyaluronic acid is coated on the surface of the nanocarrier composite material MHB NPs to form a first nanocomposite material MHB-HA NPs, and the average particle size of the first nanocomposite material MHB-HA NPs is 280-300 nm; Or, The targeting peptide RGD is coated on the surface of the nanocarrier composite material MHB NPs to form a second nanocomposite material MHB-RGD NPs, and the average particle size of the second nanocomposite material MHB-RGD NPs is 280-300 nm.

[0014] Preferably, the first nanocomposite material MHB-HA NPs is used for specifically targeting tumor cells with overexpressed CD44 receptors; The second nanocomposite material MHB-RGD NPs is used for actively targeting integrins on the surface of tumor cells.

[0015] A second aspect of the present invention provides a preparation method of a MOF composite material, comprising: Dissolve hypocrellin B or a derivative of hypocrellin B in a solvent to form a hypocrellin B solution or a hypocrellin B derivative solution; Add the metal-organic framework material MIL-100(Fe) to the hypocrellin B solution or the hypocrellin B derivative solution, stir and centrifuge to obtain the nanocarrier composite material MHB NPs.

[0016] Preferably, the preparation method of the metal-organic framework material MIL-100(Fe) comprises: Dissolve trimesic acid in an alkaline solution to obtain a first solution; Dissolve the iron source containing Fe 2+ in water to obtain a second solution; Drop the first solution into the second solution, stir, and centrifuge to obtain the metal-organic framework material MIL-100(Fe).

[0017] Preferably, the preparation method further includes: Coat the surface of the nanocarrier composite material MHB NPs with a targeting drug, and the targeting drug includes hyaluronic acid, folic acid, or the targeting peptide RGD.

[0018] Preferably, dissolve the hyaluronic acid in water to obtain an aqueous hyaluronic acid solution; Add the aqueous hyaluronic acid solution into the nanocarrier composite material MHB NPs, stir, and centrifuge to obtain the first nanocomposite material MHB-HA NPs; wherein, the mass ratio of the metal-organic framework material MIL-100(Fe) to the hyaluronic acid in the nanocarrier composite material MHB NPs is 1:(0.25~1.5).

[0019] Preferably, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and the nanocarrier composite material MHB NPs into water to obtain an activated aqueous solution of MHB NPs; Then add the targeting peptide RGD into the activated aqueous solution of MHB NPs, let it stand, and centrifuge to obtain the second nanocomposite material MHB-RGD NPs; wherein, the mass ratio of the nanocarrier composite material MHB NPs to the targeting peptide RGD is (3~8):(0.5~2).

[0020] According to the MOF composite material and its preparation method provided by the present invention, the MOF composite material uses the metal-organic framework material MIL-100(Fe) as a drug carrier, and loads hypocrellin B (HB) or a derivative of hypocrellin B on the drug carrier to form a nanocarrier composite material MHB NPs, which is beneficial to the treatment of tumor cells with red light.

[0021] Further, the surface of the nano-carrier composite material MHB NPs is coated with targeting drugs such as hyaluronic acid, folic acid or targeting peptide RGD, etc.; coating the targeting molecule hyaluronic acid on the surface of MHB NPs can prepare the first nano-composite material MHB-HA NPs with active targeting property. The obtained first nano-composite material MHB-HA NPs is safe for cell lines and can specifically target malignant tumor cells with overexpression of CD44 receptor. Coating the targeting peptide RGD on the surface of MHB NPs can prepare the second nano-composite material MHB-RGD NPs with active targeting property. The second nano-composite material MHB-RGDNPs can specifically bind to integrins such as α v β3, α v β5, etc., enabling the targeting drug to be accurately positioned on the surface of tumor cells, thereby enhancing the therapeutic effect and reducing side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Other features, objects and advantages of the present application will become more apparent by reading the following detailed description of non-limiting embodiments with reference to the accompanying drawings: Figure 1 It is the ultraviolet-visible absorption spectrogram of hypocrellin B and its derivatives provided by the embodiment of the present application; Figure 2 It is the color comparison diagram of the supernatant before and after the metal-organic framework material MIL-100(Fe) adsorbs the hypocrellin B derivative HB2 provided by the embodiment of the present application; Figure 3 It is the ultraviolet absorption standard curve diagram provided by the embodiment of the present application; Figure 4 It is the XRD diagram of the synthesized MIL-100(Fe) and the calculated MIL-100(Fe) provided by the embodiment of the present application; Figure 5 It is the particle size and potential diagram of MIL-100(Fe) and MOF-HA NPs with different HA contents provided by the embodiment of the present application; Figure 6 It is the particle size distribution diagram of MIL-100(Fe) and MOF-HA NPs provided by the embodiment of the present application; Figure 7 It is the scanning electron microscope diagram of MIL-100(Fe), MHB NPs and MHB-HA NPs provided by the embodiment of the present application; Figure 8 It is the infrared spectrogram of MIL-100(Fe), MHB NPs and MHB-HA NPs provided by the embodiment of the present application; Figure 9Cell viability graphs of HB2, MHB-HA, and MHB-HA + H2O2 provided in the embodiments of the present application after treating Hela cells for 24 hours; wherein, the concentration of H2O2 is 0.5 μmol / L; Figure 10 Cell viability graphs of MIL-100(Fe), HA, and MHB-HA NPs materials provided in the embodiments of the present application after treating Hela cells for 24 hours; Figure 11 Release graphs of HB2 in MHB-HA NPs under light and dark conditions provided in the embodiments of the present application; Figure 12 Cell viability graphs of different materials after co-incubating with Hela cells provided in the embodiments of the present application; Figure 13 Cell viability graphs of MHB-HA NPs after co-incubating with Hela cells and irradiating with laser for different times provided in the embodiments of the present application; Figure 14 Potential graphs of MIL-100(Fe) and MOF-RGD NPs provided in the embodiments of the present application; Figure 15 Particle size graphs of MIL-100(Fe) and MOF-RGD NPs provided in the embodiments of the present application; Figure 16 Cell viability graphs of different materials after co-incubating with Huvec cells under laser irradiation provided in the embodiments of the present application.

[0023] In the above figures, both MHB NPs and MHB-HA NPs use the derivative HB2, and MHB-HA NPs use MHA3. Detailed implementation manners

[0024] The present application will be further described in detail below with reference to the accompanying drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the related invention and are not intended to limit the invention. Additionally, it should be noted that for the convenience of description, only the parts related to the invention are shown in the drawings.

[0025] It should be noted that, without conflict, the embodiments in the present application and the features in the embodiments can be combined with each other. The present application will be described in detail below with reference to the drawings and embodiments.

[0026] The terms used in this application are for the purpose of describing particular embodiments only and are not intended to limit the application. The singular forms "a", "the", and "said" used in this application and the appended claims are also intended to include the plural forms unless the context clearly dictates otherwise. It should also be understood that the term "and / or" used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.

[0027] Unless the context otherwise requires, throughout the specification and claims, the term "comprising" is to be construed in an open, inclusive sense, i.e., "including, but not limited to".

[0028] In the description of the specification, the terms "one embodiment", "some embodiments", "exemplary embodiments", "examples", "specific examples", or "some examples", etc. are intended to indicate that the specific features, structures, materials, or characteristics related to the embodiment or example are included in at least one embodiment or example of the present disclosure. The schematic representations of the above terms do not necessarily refer to the same embodiment or example. In addition, the specific features, structures, materials, or characteristics may be included in any one or more embodiments or examples in any suitable manner.

[0029] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the embodiments of the present disclosure, unless otherwise specified, the meaning of "a plurality" is two or more.

[0030] In a first aspect of the embodiments of the present application, there is provided a MOF composite material, comprising: a metal-organic framework material MIL-100(Fe) and a drug carrier, wherein the drug carrier is loaded on the metal-organic framework material MIL-100(Fe) to form a nanocarrier composite material MHB NPs, and the drug carrier comprises hypocrellin B (HB) or a derivative of hypocrellin B.

[0031] Hypocrellin is a natural photosensitizer, including hypocrellin A and hypocrellin B (HB). Among them, hypocrellin A can be converted to HB under alkaline conditions. Hypocrellin is one of the polycyclic quinone pigments isolated from the traditional Chinese medicine bamboo shoots and has been widely used as a photoactive substance. As a new type of natural photosensitizer, the medicinal value of hypocrellin and its derivatives is mainly manifested in aspects such as anti-inflammatory, analgesic, antibacterial, and anti-tumor. Compared with other existing phototherapy drugs, it has the advantages of simple preparation and purification, strong near-infrared absorption, large molar extinction coefficient, strong phototoxicity, low dark toxicity, and rapid in vivo metabolism. The biggest advantage is that it is easy to be modified to obtain pure monomer derivatives. However, due to its weak absorption within the phototherapy window (600 - 900 nm), hypocrellin is not suitable for the phototherapy of solid tumors. As a lipophilic organic compound, hypocrellin can promote cell uptake, but it has an inhibitory effect on drug delivery, resulting in poor bioavailability and non-specific tissue distribution. To address these limitations, relevant research is carried out through strategies such as chemical modification or constructing new nanostructures by compounding with inorganic nanomaterials to improve the bioavailability and efficacy of hypocrellin.

[0032] Metal-organic framework material MIL-100(Fe), as a drug carrier, is the core of drug delivery technology. A drug carrier has the property of being able to transport and release drugs at a specified target site and can be a porous material, nanoparticle, lysosome, or some other carrier. In recent years, with the rapid development of nanotechnology, many nanomaterials have been synthesized and applied in various fields, including biomedical imaging, biosensing, disease diagnosis, and treatment. Especially in the biomedical field, compared with traditional drugs, nanodrugs can reduce side effects and improve utilization. Therefore, nanotherapy can not only overcome the obstacles of traditional drugs but also has great potential to meet the future market demand for tumor disease treatment. Thus, new nanodrugs are further developed to meet the growing demand for tumor treatment.

[0033] Due to the unique physical and chemical properties of nanoparticles, nanocarriers can target and deliver drugs to the target site, and significantly improve the pharmacokinetics of drugs. Currently, the research on nanoscale metal-organic frameworks (nMOFs) is relatively hot. Metal-organic frameworks have been used as nanocarriers for delivering anticancer drugs such as doxorubicin and cisplatin, as well as other agents for biomedical cancer treatment such as near-infrared organic dyes and photosensitizers. nMOFs are constructed by the coordination interaction between inorganic units containing metals and organic polycomplex linkers. nMOFs have a wide range of applications in gas storage and separation, catalysis, luminescence, drug delivery, and 3D printing. This is because nMOFs have the following advantages: the components of nMOFs are adjustable, which is beneficial for introducing multiple treatment regimens in tumor treatment; the high porosity of nMOFs provides a nanoscale platform for the storage and delivery of various drugs, thus allowing the combined application of multiple treatment methods; the functionalization of nMOFs allows for active or passive targeting and enrichment in tumor tissues to achieve the purpose of targeted tumor treatment. Based on these advantages, nMOF-based nanodrugs are becoming a new cancer treatment strategy in cancer treatment.

[0034] In recent years, the most widely studied MOF material is MIL-100(Fe), which is an octahedral structure composed of Fe 3+ and trimesic acid. MIL-100(Fe) has excellent thermal stability, adsorption performance, and photocatalytic performance. It remains structurally stable even after being exposed to boiling water for several weeks and is one of the thermodynamically stable MOFs. In addition, due to its high specific surface area, high porosity, two different microporous windows (2.5 and 2.9 μm), and stability in the biological environment, it has been widely studied as a drug carrier. As a heterogeneous catalyst, iron-based MOF materials can not only be excited by visible light / ultraviolet light to generate photogenerated electrons and holes, showing catalytic performance, but also can construct a Fenton-like system with H2O2 to catalyze the rapid decomposition of H2O2 to produce hydroxyl radicals (·OH). Therefore, loading photosensitizers in MIL-100(Fe) NPs can combine phototherapy with chemodynamic therapy (CDT) through the Fenton-like reaction to achieve good anti-tumor effects.

[0035] In the embodiments of this application, using the metal-organic framework material MIL-100(Fe) as a drug carrier, hypocrellin B (HB) or a derivative of hypocrellin B is loaded on the drug carrier to form a nanocarrier composite MHB NPs, which is beneficial for treating tumor cells with red light.

[0036] Among them, the structural formula of the hypocrellin B (HB) is:

[0037] The derivatives of hypocrellin B include: derivative HB1 or derivative HB2, and the structural formulas of the derivative HB1 and the derivative HB2 are as follows:

[0038] Wherein, Me is methyl.

[0039] Hypocrellin B (HB) is soluble in toluene and soluble in organic solvents such as ethanol, but insoluble in water. Derivative HB1 is soluble in ethanol and soluble in water. And derivative HB2 is soluble in water. The ultraviolet-visible absorption spectra of hypocrellin B (HB), derivative HB1 and derivative HB2 are as Figure 1 shown. As can be seen from Figure 1 , compared with pure hypocrellin B (HB), the modified derivatives HB1 and HB2 show extremely broad absorption in the phototherapy window (600 - 900 nm) range. Therefore, the red light range of the nanocarrier composite material MHB NPs formed by the composite of derivative HB1 and HB2 with MIL-100(Fe) is wider, which is beneficial to the treatment of tumor cells with red light. It is preferred to use HB2 to be composite with MIL-100(Fe).

[0040] In some embodiments, the drug loading of the drug-loaded carrier is 20% - 40%, wherein the drug loading of the drug-loaded carrier is the mass percentage of the drug-loaded carrier in the nanocarrier composite material MHB NPs.

[0041] Specifically, the drug loading of hypocrellin B (HB) or the derivatives of hypocrellin B in the nanocarrier composite material MHB NPs is relatively high, enhancing the drug loading capacity, therapeutic effect and sustained release ability, and having a good therapeutic effect on tumors.

[0042] In some embodiments, the average particle size of the metal-organic framework material MIL-100(Fe) is 200 - 230 nm; the average particle size of the nanocarrier composite material MHB NPs is 230 - 250 nm.

[0043] Specifically, MIL-100(Fe) serves as a nanocarrier that can target and deliver drugs to the target site and significantly improve the pharmacokinetics of the drugs. The average particle size of the nanocarrier composite MHB NPs is larger than that of the metal-organic framework material MIL-100(Fe). The average particle size of the metal-organic framework material MIL-100(Fe) is 200-230 nm, and the average particle size of the nanocarrier composite MHB NPs is 230-250 nm. Exemplarily, the average particle size of the metal-organic framework material MIL-100(Fe) is 200 nm, 210 nm, 215 nm, 220 nm, 225 nm, 230 nm, and the average particle size of the nanocarrier composite MHB NPs is 230 nm, 234 nm, 238 nm, 245 nm, 247 nm, 250 nm, etc., indicating that hypocrellin B or its derivatives are successfully loaded on the metal-organic framework material MIL-100(Fe).

[0044] In some embodiments, the MOF composite further includes a targeting drug, and the targeting drug is coated on the surface of the nanocarrier composite MHB NPs. The targeting drug includes hyaluronic acid, folic acid, or the targeting peptide RGD.

[0045] Among them, the targeting drug is coated on the surface of the nanocarrier composite MHB NPs or the surface of MIL-100(Fe). For example, hyaluronic acid is coated on the surface of MIL-100(Fe) to form MHA NPs, the targeting peptide RGD is coated on the surface of MIL-100(Fe) to form MOF-RGD NPs, hyaluronic acid is coated on the surface of the nanocarrier composite MHB NPs to form the first nanocomposite MHB-HA NPs, and the targeting peptide RGD is coated on the surface of MIL-100(Fe) to form the second nanocomposite MHB-RGDNPs.

[0046] To further obtain active targeting to tumors, MIL-100(Fe) also needs to be modified with tumor-targeting molecules. Hyaluronic acid (HA) belongs to glycosaminoglycan compounds and is an ideal tumor-targeting material. It is a hydrophilic macromolecule with carboxyl and hydroxyl functional groups. Coupling HA with the drug-loaded MOF material MHB NPs can improve the pharmacokinetic characteristics of the MOF material, extend the drug distribution and elimination time, and at the same time endow the nanocarrier composite material MHB NPs with the ability to actively target CD44-overexpressing malignant tumor cells. Therefore, in the present invention, hyaluronic acid (HA) is used to modify the surface of MHB NPs, which can be functionalized to have the ability to actively target tumors, overcome the problem of uneven biodistribution in the aqueous environment, increase cell uptake, and further improve the drug efficacy. In the present invention, HA is used as a shielding layer to wrap on the surface of MIL-100(Fe) to facilitate improving its stability and active targeting to tumors.

[0047] In this example, hyaluronic acid (HA) is a natural proteoglycan widely distributed in the extracellular matrix, connective tissue, and organs of higher animals. CD44 is the most important HA receptor on the cell surface. The binding of HA to CD44 can regulate various biological behaviors of cells, including cell adhesion, migration, proliferation, differentiation, and wound healing. Since CD44 molecules are overexpressed on the surface of tumor cells, using the high-affinity property of HA and CD44, the targeting of the carrier to tumor cells can be improved and the cytotoxicity can be reduced after modification with HA. Coating the targeting molecule hyaluronic acid (HA) on the surface of MHB NPs can prepare the first nanocomposite material MHB-HA NPs with active targeting. The obtained first nanocomposite material MHB-HA NPs is safe for cell lines and can specifically target malignant tumor cells with overexpression of the CD44 receptor.

[0048] The targeting peptide RGD is a type of polypeptide containing the tripeptide sequence of arginine-glycine-aspartic acid (Arg-Gly-Asp). It is a basic component in the structures of various biological extracellular matrices and plasma proteins and is a basic unit of the cell recognition system. It is widely present between cells and participates in various biological processes such as homeostasis regulation, phagocytosis, cell migration, and lymphocyte recognition. Since integrin α v β3 is highly expressed on the surface of tumor neovascular endothelial cells and various solid tumor cells such as melanoma and breast cancer, it is an ideal tumor treatment target, and its ligand RGD peptide can be specifically recognized by integrin α v β3. In the present invention, this property is utilized to coat RGD on the surface of the drug-loaded MOF material MHB NPs to deliver the drug to target cells, thereby achieving active targeting of tumors, increasing the uptake of the drug by tumor cells, and improving the curative effect.

[0049] In this example, the targeting peptide RGD is coated on the surface of MHB NPs, and the second nanocomposite MHB-RGD NPs with active targeting can be prepared. This second nanocomposite MHB-RGD NPs can specifically bind to integrins such as α v β3 and αvβ5 on the surface of tumor cells, enabling the targeted drug to accurately localize to the surface of tumor cells, thereby enhancing the therapeutic effect and reducing side effects. In malignant tumor cells, this second nanocomposite MHB-RGD NPs can effectively release the drug under the stimulation of the tumor microacidic environment. Under laser irradiation, the derivative of hypocrellin B can be effectively activated to achieve the synergistic treatment of tumors by photodynamic and photothermal therapies, with a small dose and good efficacy.

[0050] Folic acid is one of the essential vitamins for the human body. However, folic acid does not exist in the human body, and all the required folic acid needs to be taken in from the outside. For example, taking folic acid during pregnancy to prevent neural tube defects in newborns, and folic acid-deficient anemia patients taking folic acid to correct anemia, etc. The folic acid ingested from the outside cannot directly exert its function and needs to be mediated by folic acid receptors and transported into the cytoplasm through endocytosis. The members of the folic acid receptor family are FR α 、FR β 、FR γ and FR δ , among which FR α is the receptor most promising to become a drug target. The reason is that FR α , in addition to being able to transport folic acid, is also an accomplice of tumor cells. During the proliferation and metastasis of cancer cells, FR α also plays a role in fueling the process. Therefore, theoretically, inhibiting FR α can control the metastasis and invasion of tumors. In the embodiments of the present application, folic acid is coated on the surface of the nanocarrier composite MHB NPs to improve the targeting to tumor cells.

[0051] In some embodiments, the mass ratio of the metal-organic framework material MIL-100(Fe) to the targeted drug is 1:(0.25~1.5), and the preferred mass ratio is 1:0.75.

[0052] Exemplarily, the mass ratio of MIL-100(Fe) to hyaluronic acid (HA) can be 1:0.25, 1:0.5, 1:0.75, 1:1, 1:1.5, etc. The average particle size of the formed first nanocomposite MHB-HA NPs is 280-300 nm. Exemplarily, the average particle size of the first nanocomposite MHB-HA NPs is 280 nm, 282 nm, 285 nm, 290 nm, 293 nm, 295 nm, 300 nm, etc. When the mass ratio of MIL-100(Fe) to HA is less than 0.25, the particle size of the formed first nanocomposite MHB-HA NPs is smaller; when the mass ratio of MIL-100(Fe) to HA is greater than 1:1.5, the potential of the formed first nanocomposite MHB-HA NPs is lower. It can be understood that the average particle size of the first nanocomposite MHB-HA NPs is larger than the average particle size of MIL-100(Fe), and the average particle size of MHB-HA NPs is larger than the average particle size of MHB NPs, indicating that hypocrellin B or its derivatives are successfully loaded on MIL-100(Fe) and hyaluronic acid (HA) is loaded.

[0053] In some embodiments, the targeting peptide RGD is coated on the surface of the nanocarrier composite MHB NPs to form nanocarrier composite MHB-RGD NPs. The average particle size of the nanocarrier composite MHB-RGD NPs is 280-300 nm. Exemplarily, the average particle size of the nanocarrier composite MHB-RGD NPs is 280 nm, 285 nm, 290 nm, 295 nm, 300 nm, etc.

[0054] Specifically, the average particle size of MOF-RGD NPs (referring to the material formed by RGD coated on the surface of MIL-100(Fe)) is larger than the average particle size of MIL-100(Fe). Exemplarily, the average particle size of MOF-RGD NPs is 301 nm, slightly larger than the average particle size of unmodified MIL-100(Fe) which is 200-230 nm. This also confirms that RGD molecules have been coated on the surface of MIL-100(Fe).

[0055] In the second aspect of the embodiments of the present application, a preparation method 100 of a MOF composite material is provided, including: S110: Dissolve hypocrellin B or a derivative of hypocrellin B in a solvent to form a hypocrellin B solution or a hypocrellin B derivative solution; S120: Add the metal-organic framework material MIL-100(Fe) to the hypocrellin B solution or the hypocrellin B derivative solution, stir, and centrifuge to obtain the nanocarrier composite MHB NPs.

[0056] Exemplarily, the solvent includes water, toluene, ethanol, etc. The derivative HB1 or HB2 is dissolved in water to obtain a derivative solution of hypocrellin B; the metal-organic framework material MIL-100(Fe) is added to the derivative solution of hypocrellin B, stirred, and centrifuged to obtain the nanocarrier composite material MHB NPs. Preferably, the stirring time is 20 - 28 h, the centrifugation speed is 6000 - 10000 rpm, and the centrifugation time is 8 - 15 min.

[0057] For example, HB2 is dissolved in water to obtain a derivative solution; then MIL-100(Fe) is added to the derivative solution, and stirred in the dark at room temperature for 24 h. After stirring, the solid is collected by centrifugation at a speed of 8000 rpm for 10 min, the supernatant is aspirated and its absorbance A is measured. HB2 ; At the same time, the collected solid precipitate is dispersed in deionized water for washing, and the operation is repeated three times to obtain MHB NPs. Figure 2 It shows that the color change of the supernatant before and after adsorption is obvious. The supernatant before adsorption is black, and the supernatant after adsorption is transparent, indicating that the MIL-100(Fe) material does adsorb the derivative of the drug hypocrellin B.

[0058] The drug loading content (DLC) in the nanocarrier composite material MHB NPs is measured by an ultraviolet-visible spectrophotometer. The calculation formula of DLC (%) is as follows:

[0059] Among them, in the nanocarrier composite material MHB NPs, derivative solutions of HB2 with different known concentrations are pre-prepared, and then the absorbance corresponding to each derivative solution of HB2 with a known concentration is measured respectively by an ultraviolet-visible spectrophotometer. An ultraviolet absorption standard curve is plotted according to the concentration and absorbance corresponding to each derivative solution of HB2 with a known concentration. Exemplarily, the ultraviolet absorption standard curve is as Figure 3 shown, specifically: y = 10.04x - 7.8*10 -5 ; y represents the absorbance, and x represents the concentration. Substitute the measured absorbance A HB2 into the ultraviolet absorption standard curve to obtain the concentration of the HB2 derivative solution in the supernatant. Multiply the concentration of the HB2 derivative solution in the supernatant by its volume to obtain the mass of HB2.

[0060] The total mass of MHB NPs is the sum of the mass of HB2 and the mass of MIL-100(Fe). According to the mass of HB2 and the total mass of MHB NPs and in combination with the above formula, the drug loading content of HB2 in MHB NPs is calculated. Exemplarily, the drug loading content of HB2 is 29.12%.

[0061] The calculation method of the drug loading amount of HB1 in MHB NPs is the same as that of HB2, which will not be elaborated in this application.

[0062] In some embodiments, before S110, the preparation method of the metal-organic framework material MIL-100(Fe) includes: S101: Dissolve trimesic acid in an alkaline solution to obtain a first solution.

[0063] The alkaline solution includes sodium hydroxide (NaOH) solution, potassium hydroxide (KOH) solution, etc. The mass ratio of trimesic acid (H3BTC) to the alkaline solution is (1~3):(40~60).

[0064] S102: Dissolve the iron source containing Fe 2+ in water to obtain a second solution.

[0065] The iron source containing Fe 2+ includes ferrous sulfate heptahydrate (FeSO4·7H2O), ferrous chloride tetrahydrate (FeCl2·4H2O), etc. The mass ratio of the iron source containing Fe 2+ to water is (1~5):(100~140).

[0066] S103: Drop the first solution into the second solution, stir for 18~30 h, and centrifuge at a speed of 6000~10000 rpm for 8~15 min to obtain the metal-organic framework material MIL-100(Fe).

[0067] Exemplarily, 1.597 g (7.6 mmol) of H3BTC was dissolved in 48.56 g of 1 M NaOH aqueous solution (22.8 mmol) to obtain a first solution with a pH of about 11. 2.26 g (11.4 mmol) of FeCl2·4H2O was dissolved in 120.38 g of H2O to obtain a second solution with a pH of about 2.7. After the two solutions of the first solution and the second solution were dissolved until completely transparent and without precipitation, a clean beaker was taken and the first solution was slowly added dropwise to the second solution under magnetic stirring at a molar ratio of the mixture of Fe:H3BTC:NaOH:H2O = 1.5 mol:1.0 mol:3.0 mol:880 mol. At this time, it could be observed that a gray-green precipitate was immediately formed in the beaker, and the pH of the solution was measured with a pH meter to be approximately 5.2. After all of the first solution was added to the second solution, stirring was continued at room temperature for 24 h. After the stirring was completed, centrifugation was carried out at a speed of 8000 rpm for 10 min, the solid sample was collected, the supernatant was discarded, and the obtained solid was transferred to a mixed solution of ethanol:water = 1:1 (volume ratio), and then heated and washed in a water bath at 90 °C, and centrifuged and collected after repeating three times. The collected solid precipitate was placed in an oven at 80 °C and dried overnight, and then ground and dried in a vacuum oven at 120 °C for 6 h to finally obtain a red-brown powdered solid, namely MIL-100(Fe).

[0068] In the embodiment of the present application, MIL-100(Fe) was synthesized by a green method without using any toxic solvents. In this method, Fe 2+ was used as the main source of iron, which was gradually oxidized to Fe 3+ resulting in the formation of the MIL-100(Fe) structure under distilled water and room temperature conditions. Figure 4 shows the X-ray diffraction (XRD) analysis results of the MIL-100(Fe) structure at 5 to 30 ° (2θ) and the calculated XRD of MIL-100(Fe) (from the cif file). Figure 4 The comparison between the synthesized structure and the calculated structure of MIL-100(Fe) in [reference] shows that the structure was well synthesized. Among them, 2θ refers to the angle between the incident X-ray beam and the diffraction detector. The X-ray emitted by the X-ray source is incident on the sample at a certain angle (θ) and diffracts on the crystal plane of the sample, and the diffracted X-ray is received by the detector at a certain angle (θ). The incident angle and the diffraction angle are each θ, jointly forming the angle 2θ.

[0069] In this example, a MIL-100(Fe) material with a high drug loading capacity was synthesized in an aqueous medium at room temperature without using any harmful solvents to enhance the drug loading capacity, therapeutic effect, and sustained release ability, and the synthesized MIL-100(Fe) material has a good structure. MIL-100(Fe) decomposes in the mildly acidic environment of tumors, and the released Fe 3+ will further neutralize the excessive glutathione in the tumor microenvironment, weaken the reduction effect on reactive oxygen species (ROS), thereby improving the efficacy of photodynamic therapy, and at the same time reducing to obtain Fe 2+ , triggering the occurrence of the Fenton-like reaction, further synergizing phototherapy and chemodynamic therapy to cause more efficient generation of excessive lipid peroxidation in cells, thereby inducing cell death.

[0070] In some embodiments, the preparation method 100 of the MOF composite material further includes: S130: Coating the targeted drug on the surface of the nanocarrier composite material MHB NPs, and the targeted drug includes hyaluronic acid, folic acid, or the targeting peptide RGD.

[0071] Exemplarily, dissolve hyaluronic acid (HA) in water, then add HA with different mass ratios to MIL-100(Fe) into the MHB NPs solution, stir at room temperature in the dark for 30 minutes, after stirring, centrifuge at 9000 rpm for 15 min to collect the solid, suck out the supernatant, disperse the collected solid precipitate in deionized water for washing, and repeat three times to remove free HA, finally obtaining the first nanocomposite material MHB-HA NPs, and disperse it in deionized water by ultrasonic dispersion method for subsequent experiments.

[0072] Among them, the mass ratio of MIL-100(Fe) to HA is 1:(0.25~1.5). Exemplarily, five kinds of HA with different mass ratios to MIL-100(Fe) are respectively MHA1: MIL-100(Fe) / HA (w / w)=1 / 0.25; MHA2: MIL-100(Fe) / HA (w / w)=1 / 0.5; MHA3: MIL-100(Fe) / HA (w / w)=1 / 0.75; MHA4: MIL-100(Fe) / HA (w / w)=1 / 1; MHA5: MIL-100(Fe) / HA (w / w)=1 / 1.5.

[0073] Coat the above five kinds of HA with different mass ratios on the surface of MIL-100(Fe) to form MHA NPs with different mass ratios of HA, and test the particle size and potential of MHA NPs and MIL-100(Fe). The test results are as Figure 5 andFigure 6 As shown, by Figure 5 It can be seen that with the increase of HA content, the particle size of MHA NPs gradually increases and the zeta potential gradually decreases. Based on the above results, it is concluded that the optimal modification mass ratio of MIL-100(Fe) to HA is 1:0.75, with a narrow particle size dispersity and appropriate potential. The particle size of MHA NPs is 285 nm, and the zeta potential of MHA NPs is -48.6 mV (known from Figure 5 and Figure 6 ). Compared with MIL-100(Fe), the absolute value of its surface potential increases because the coating of HA increases the stability of the nanoparticles.

[0074] The materials of MIL-100(Fe), MHB NPs and MHB-HA NPs were further characterized by scanning electron microscopy. The scanning electron microscopy analysis results are as shown in Figure 7 . The corresponding loaded drug in MHB NPs and MHB-HA NPs is HB2. It can be seen from Figure 7 that these materials of MIL-100(Fe), MHB NPs and MHB-HA NPs all show irregular polyhedron shapes, with uniform sizes and a particle size of about 200 nm. Figure 7 shows that the particle size characterized by scanning electron microscopy is smaller than that measured by the particle size analyzer. The reason is that the nano-particle states of the two are different. The particle size observed by scanning electron microscopy is the particle size of the dry particles adhered to the silicon wafer surface, while the sample of the particle size analyzer is measured after being dispersed in the liquid, and the measured is the equivalent particle size of the particles in the water medium, which includes both the particle size of the particles themselves and the thickness of the hydration layer, so it is larger. The scanning electron microscopy image shows that the edges of the nanoparticles become clear and the dispersibility is improved after the surface modification of HA.

[0075] The materials of MIL-100(Fe), MHB NPs and MHB-HA NPs were tested by infrared spectroscopy. The corresponding loaded drug in MHB NPs and MHB-HA NPs is HB2. The infrared spectrum results are as shown in Figure 8 . It can be seen from Figure 8 that compared with MIL-100(Fe), the composite materials MHB NPs and MHB-HA NPs show peaks at 1225 cm -1 . This indicates the appearance of ether bonds, and there happens to be ether bonds in HB2, indicating that the drug HB2 is successfully loaded into the pores of MIL-100(Fe).

[0076] Experiment 1 In vitro dark toxicity test of MHB-HA NPs To better evaluate the biosafety of the material, the CCK-8 method was used to detect its viability after co-incubation with Hela cells for 24 hours. Hela cells were placed in a 96-well plate, 5*10 3 cells per well. After culturing for 12 h, the cells were treated with different concentrations of the material, and complete medium was used as a control. After incubation for 24 hours, the cells were washed twice with PBS, then 1 mL of complete medium containing CCK-8 (10%) was added, and incubation was continued for 0.5 - 4 hours. Finally, the absorbance at 450 nm was measured using a microplate reader.

[0077] Cell viability (%) = (A1 - A0) / (A2 - A0) × 100% where A1 is the absorbance of the sample group, A2 is the absorbance of the control group, and A0 is the blank.

[0078] The cell viability test results corresponding to different concentrations of the material are as Figure 9 and Figure 10 shown. Figure 9 They are the cell viabilities of HB2, MHB-HANPs, and MHB-HA NPs + 0.5 μmol / L H2O2 at concentrations of 0.5 mg / L, 1 mg / L, 2 mg / L, 5 mg / L, 10 mg / L, and 15 mg / L respectively. The loaded drug in MHB-HA NPs is HB2, and MHA3 is the corresponding mass ratio. From Figure 9 it can be seen that without laser irradiation, HB2 does not cause damage to cells. When co-incubating cells with low-concentration (0.5 - 15 mg / L) MHB-HANPs solution, adding H2O2 also does not cause damage to cells because the concentration of Fe ions decomposed from MIL-100(Fe) under this condition does not reach the level that can cause ferroptosis in cells.

[0079] Figure 10 They are the cell viabilities of MIL-100(Fe), HA, and MHB-HA NPs at concentrations of 25 mg / L, 50 mg / L, 75 mg / L, 100 mg / L, and 200 mg / L respectively. The loaded drug in MHB-HA NPs is HB2. From Figure 10 it can be seen that even at a concentration as high as 200 mg / L, free HA, MIL-100(Fe) NPs, and MHB-HA NPs show negligible dark cytotoxicity to cells, indicating that HA, MIL-100(Fe) NPs, and MHB-HA NPs have high biocompatibility and can be applied in vivo.

[0080] Experiment 2 In vitro phototoxicity test of MHB-HA NPs: (1)Cell seeding: When the cell density reaches 80% of the bottom area of the culture dish, wash twice with PBS, add 1 mL of trypsin and digest for 1 min, then add 2 mL of complete medium to terminate digestion. Collect the cell suspension into a 15 mL centrifuge tube, centrifuge at 1200 rpm for 3 min. After centrifugation, discard the supernatant, add 2 mL of complete medium to resuspend and count the cells. Seed 96-well plates with 8×10 3 cells per well and 100 µL of complete medium. (2)Material treatment: Incubate for 12 h until the cells are completely adherent. Aspirate the old complete medium, add different concentrations of MHA NPs + 0.5 μmol / L H2O2, MHB-HA NPs, MHB-HA NPs + 0.5 μmol / L H2O2, MHB-HA NPs + 0.25 μmol / L H2O2, and HB2 prepared with complete medium, and continue to incubate for 4 h. Then rinse twice with PBS, change to fresh complete medium, and irradiate with a laser at 660 nm and 0.5 W cm -2 for 10 min, and then place in an incubator and continue to culture for 20 h; the corresponding loaded drug in MHB-HA NPs is HB2, and the mass ratio of MHA3. (3)Detection and analysis: After co-incubation for 24 h, wash twice with PBS, add 100 µL of CCK-8 working solution (CCK-8 stock solution: complete medium = 1:9) to each well. After incubation for 1 h, measure the OD value of each well at 450 nm, analyze and process the data, and then plot the graph. The experimental results are as Figures 11 to 13 shown.

[0081] Figure 11 is the drug HB2 release curve of MHB-HA NPs under laser and non-laser conditions (pH = 5.5, PBS). As Figure 11 can be seen, under non-laser conditions, the drug HB2 in MHB-HA NPs is released slowly; the drug HB2 in MHB-HA NPs is released faster under laser irradiation. Since MHB-HA NPs can not only slowly release HB2, but also release iron ions through the decomposition of MOFs to further initiate a Fenton-like reaction to generate hydroxyl radicals, therefore, the effects of MHB-HA NPs combined with photodynamic therapy, photothermal therapy, and chemodynamic therapy under different conditions were studied at the cellular level.

[0082] Figure 12 is the cell viability graph after co-incubation of different materials with Hela cells under laser irradiation. Figure 13 is the cell viability of MHB-HA NPs after co-incubation with Hela cells at different laser irradiation times. Place Hela cells in 96-well plates, 5×10 3Incubate overnight. After the cells adhered to the wall, treat the cells with materials at different concentrations. The laser irradiation group was treated with laser (660 nm) 4 hours after adding the composite material. After continuing to incubate for 24 hours, wash twice with PBS, then add 100 μL of complete medium containing CCK-8 (10%), and incubate for another 0.5 - 4 hours. Finally, use a microplate reader to measure the absorbance at 450 nm.

[0083] After laser irradiation was given 4 h after incubation of the MHB-HA NPs composite material with the cells, the cell viability decreased significantly. Even when the concentration was as low as 2 mg / L and irradiated with light for 10 min, more than 60% of the cells died. The cytotoxicity of the MHB-HA NPs composite material can be enhanced by increasing H2O2, which is due to the generation of hydroxyl radicals through the Fenton-like reaction in the presence of H2O2. Even at a low concentration of 1 mg / L, 90% of the cells can be killed. These results indicate that the MHB-HA NPs composite material can achieve a highly efficient anti-tumor effect through the synergistic effects of PDT, PTT, and CDT, and has great anti-tumor ability in vivo. It is worth noting that when co-incubating with cells using MHA NPs without adsorbed drugs, the effect of ferroptosis is not so obvious. However, when H2O2 is added to the MHB-HA NPs composite material after adsorbing drugs, the effect of ferroptosis is very obvious. We speculate that the presence of HB can accelerate the decomposition of MOF under light. Figure 11 The results of the in vitro release curve also prove this speculation.

[0084] In some embodiments, the RGD peptide is immobilized on the surface of MHB NPs using the coupling agents 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Add EDC, NHS, and the prepared MHB NPs to water and sonicate to obtain an aqueous solution of activated MHB NPs; then add the RGD peptide to the aqueous solution of activated MHB NPs, let it stand, and centrifuge to obtain the second nanocomposite MHB-RGD NPs; wherein, the mass ratio of EDC, NHS, and MHB NPs is (2 - 8):(1 - 4):(2 - 8); the mass ratio of MHB NPs to the RGD peptide is (3 - 8):(0.5 - 2); the sonication time is 0.5 - 2 h, the standing time is 8 - 24 h, the centrifugation speed is 6000 - 12000 rpm, and the centrifugation time is 10 - 20 min.

[0085] Exemplarily, first, EDC (5.0 mg), NHS (2.5 mg) and the prepared MHB NPs (5.0 mg) were added to deionized water (10.0 mL), and ultrasonicated for 1 h. After the reaction, RGD (1.5 mg) was added to the activated aqueous solution of MHB NPs, and left standing overnight. After completion, the solid was collected by centrifugation at 9000 rpm for 15 min, and small molecules such as residual EDC, NHS, and RGD in the supernatant were discarded. Then it was washed three times with deionized water. After the washing was completed, the solid precipitate was collected and placed in a vacuum blast dryer at 40 °C for drying, thus obtaining the second nanocomposite MHB-RGD NPs.

[0086] The Zeta potential and particle size of MIL-100(Fe) and MOF-RGD NPs were measured using a zeta potential and particle size analyzer, and the test results are as Figure 14 and Figure 15 shown. As Figure 14 can be seen, the potential of MIL-100(Fe) was -29.40 ± 1.95 mV, and the potential of MOF-RGD NPs was -12.36 ± 0.96 mV. The different potentials of the two indicate that the targeting peptide RGD has been immobilized on the surface of MIL-100(Fe).

[0087] As Figure 15 shown, the average particle size of MOF-RGD NPs measured by Dynamic Light Scattering (DLS) was 301 nm, slightly larger than the average particle size of unmodified MIL-100(Fe), which also confirmed that the targeting peptide RGD has been coated on the surface of MIL-100(Fe).

[0088] Experiment 3 In vitro phototoxicity test of MHB-RGD NPs: (1) Inoculating cells: When the cell density reached 80% of the bottom area of the culture dish, it was washed twice with PBS, then 1 mL of trypsin was added for digestion for 1 min, and then 2 mL of complete medium was added to terminate the digestion. The cell solution was collected into a 15 mL centrifuge tube, centrifuged at 1200 rpm for 3 min. After centrifugation, the supernatant was discarded, and it was resuspended with 2 mL of complete medium and counted. 96-well plates were seeded with 8×10³ cells per well and 100 µL of complete medium. (2)Material treatment: Incubate for 12 h. After the cells are completely adherent, aspirate and discard the old complete medium, add different concentrations of MOF-RGD NPs + 0.5 μmol / L H2O2, MHB-RGD NPs, MHB-RGD NPs + 0.5 μmol / L H2O2, and HB2 prepared with the complete medium, and continue to incubate for 4 h. Then rinse twice with PBS, change to a new complete medium, and irradiate with a laser at 660 nm and 0.5 W cm-2 for 10 min, and then place in an incubator and continue to culture for 20 hours. (3)Detection and analysis: After co-incubation for 24 h, wash twice with PBS, add 100 μL of CCK-8 working solution (CCK-8 stock solution: complete medium = 1:9) to each well. After incubation for 1 h, measure the OD value of each well at 450 nm, analyze and process the data and then plot the graph. The results are as Figure 16 shown.

[0089] As Figure 16 can be seen, after the second nanocomposite MHB-RGD NPs is incubated with cells for 4 h and then irradiated with a laser, the cell viability decreases significantly. Even when the concentration is as low as 0.5 mg / L and irradiated for 10 min, more than 60% of the cells die. The cytotoxicity of the MHB-RGD NPs composite can be enhanced by increasing H2O2, which is due to the generation of hydroxyl radicals through the Fenton-like reaction in the presence of H2O2. These results indicate that the MHB-RGD NPs composite can achieve an efficient anti-tumor effect through the synergistic effects of PDT, PTT, and CDT, and has great anti-tumor ability in vivo.

[0090] The above description is only the preferred embodiment of the present application and the explanation of the applied technical principles. Those skilled in the art should understand that the scope of the invention involved in the present application is not limited to the technical solutions formed by the specific combination of the above technical features, but should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the inventive concept. For example, the technical solutions formed by mutually replacing the above features with the (but not limited to) technical features with similar functions disclosed in the present application.

Claims

1. A MOF composite material, characterized in that, Comprising: A metal-organic framework material MIL-100(Fe) and a drug carrier, wherein the drug carrier is loaded on the metal-organic framework material MIL-100(Fe) to form a nano-carrier composite material MHB NPs, and the drug carrier includes hypocrellin B (HB) or a derivative of hypocrellin B.

2. The MOF composite material according to claim 1, wherein The structural formula of the hypocrellin B (HB) is: The derivatives of hypocrellin B include: derivative HB1 or derivative HB2, and the structural formulas of the derivative HB1 and the derivative HB2 are: Wherein, Me is methyl.

3. The MOF composite material according to claim 1, wherein The drug loading of the drug carrier is 20% to 40%, wherein the drug loading of the drug carrier is the mass ratio of the drug carrier in the nano-carrier composite material MHB NPs.

4. The MOF composite material according to claim 1, wherein The average particle size of the metal-organic framework material MIL-100(Fe) is 200 to 230 nm; the average particle size of the nano-carrier composite material MHB NPs is 230 to 250 nm.

5. The MOF composite material according to claim 1, wherein The MOF composite material further includes a targeted drug, the targeted drug is coated on the surface of the nano-carrier composite material MHB NPs, and the targeted drug includes hyaluronic acid, folic acid or the targeting peptide RGD.

6. The MOF composite material according to claim 5, wherein The mass ratio of the metal-organic framework material MIL-100(Fe) to the hyaluronic acid is 1:(0.25 to 1.5); Or, The mass ratio of the nano-carrier composite material MHB NPs to the targeting peptide RGD is (3 to 8):(0.5 to 2).

7. The MOF composite material according to claim 5, wherein, The hyaluronic acid is coated on the surface of the nano-carrier composite material MHB NPs to form a first nano-composite material MHB-HA NPs, and the average particle size of the first nano-composite material MHB-HA NPs is 280 to 300 nm; Or, The targeting peptide RGD is coated on the surface of the nano-carrier composite material MHB NPs to form a second nano-composite material MHB-RGD NPs, and the average particle size of the second nano-composite material MHB-RGD NPs is 280 to 300 nm.

8. The MOF composite material according to claim 7, wherein The first nano-composite material MHB-HANPs is used for specifically targeting tumor cells with overexpression of CD44 receptor; The second nano-composite material MHB-RGD NPs is used for actively targeting integrin on the surface of tumor cells.

9. A preparation method of a MOF composite material, characterized in that, Comprising: Dissolving hypocrellin B or a derivative of hypocrellin B in a solvent to form a hypocrellin B solution or a hypocrellin B derivative solution; Adding the metal-organic framework material MIL-100(Fe) into the hypocrellin B solution or the hypocrellin B derivative solution, stirring, and centrifuging to obtain the nano-carrier composite material MHB NPs.

10. The preparation method of the MOF composite material according to claim 9, characterized in that, The preparation method of the metal-organic framework material MIL-100(Fe) includes: Dissolving trimesic acid in an alkaline solution to obtain a first solution; Dissolve the iron source containing Fe 2+ in water to obtain a second solution; Dropping the first solution into the second solution, stirring, and centrifuging to obtain the metal-organic framework material MIL-100(Fe).

11. The preparation method of the MOF composite material according to claim 9 or 10, characterized in that, The preparation method further includes: Coat the surface of the nanocarrier composite MHB NPs with a targeted drug, where the targeted drug includes hyaluronic acid, folic acid, or the targeting peptide RGD.

12. The preparation method of the MOF composite material according to claim 11, characterized in that, Dissolve the hyaluronic acid in water to obtain an aqueous hyaluronic acid solution. Add the aqueous hyaluronic acid solution into the nanocarrier composite MHB NPs, stir, and centrifuge to obtain the first nanocomposite MHB-HA NPs; wherein, the mass ratio of the metal-organic framework material MIL-100(Fe) to the hyaluronic acid in the nanocarrier composite MHB NPs is 1:(0.25 - 1.5).

13. The preparation method of the MOF composite material according to claim 11, wherein, Add 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and the nanocarrier composite MHB NPs into water to obtain an activated MHB NPs aqueous solution. Then add the targeting peptide RGD into the activated MHB NPs aqueous solution, let it stand, and centrifuge to obtain the second nanocomposite MHB-RGD NPs; wherein, the mass ratio of the nanocarrier composite MHB NPs to the targeting peptide RGD is (3 - 8):(0.5 - 2).

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